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    COMPOSITIONS AND METHODS FOR THE BIOSYNTHESIS OF 1,4-BUTANEDIOL AND ITS PRECURSORS
    22.
    发明公开
    COMPOSITIONS AND METHODS FOR THE BIOSYNTHESIS OF 1,4-BUTANEDIOL AND ITS PRECURSORS 有权
    组合物和生物合成1,4-丁二醇及其前体的方法

    公开(公告)号：EP2137315A2

    公开(公告)日：2009-12-30

    申请号：EP08732315.0

    申请日：2008-03-14

    Applicant: Genomatica, Inc.

    Inventor： BURK, Mark, J. ,  VAN DIEN, Stephen, J. ,  BURGARD, Anthony ,  NIU, Wei

    IPC: C12P1/00

    CPC classification number: C12N15/52 ,  B01D3/002 ,  C12N9/0006 ,  C12N9/0008 ,  C12N9/88 ,  C12N9/93 ,  C12N15/70 ,  C12N15/81 ,  C12P7/18 ,  C12P7/42 ,  C12P7/52 ,  C12P17/04 ,  C12Y101/01061 ,  C12Y102/01076 ,  C12Y401/01071 ,  C12Y602/01004 ,  Y02P20/52

    Abstract: The invention provides a non-naturally occurring microbial biocatalyst including a microbial organism having a 4-hydroxybutanoic acid (4-HB) biosynthetic pathway having at least one exogenous nucleic acid encoding 4-hydroxybutanoate dehydrogenase, succinyl-CoA synthetase, CoA-dependent succinic semialdehyde dehydrogenase, or ±-ketoglutarate decarboxylase, wherein the exogenous nucleic acid is expressed in sufficient amounts to produce monomeric 4-hydroxybutanoic acid (4-HB). Also provided is a non-naturally occurring microbial biocatalyst including a microbial organism having 4-hydroxybutanoic acid (4-HB) and 1,4-butanediol (BDO) biosynthetic pathways, the pathways include at least one exogenous nucleic acid encoding 4-hydroxybutanoate dehydrogenase, succinyl-CoA synthetase, CoA-dependent succinic semialdehyde dehydrogenase, 4-hydroxybutyrate:CoA transferase, 4-butyrate kinase, phosphotransbutyrylase, ±-ketoglutarate decarboxylase, aldehyde dehydrogenase, alcohol dehydrogenase or an aldehyde/alcohol dehydrogenase, wherein the exogenous nucleic acid is expressed in sufficient amounts to produce 1,4-butanediol (BDO). Additionally provided is a method for the production of 4-HB. The method includes culturing a non-naturally occurring microbial organism having a 4-hydroxybutanoic acid (4-HB) biosynthetic pathway including at least one exogenous nucleic acid encoding 4-hydroxybutanoate dehydrogenase, succinyl-CoA synthetase, CoA-dependent succinic semialdehyde dehydrogenase or ±-ketoglutarate decarboxylase under substantially anaerobic conditions for a sufficient period of time to produce monomeric 4-hydroxybutanoic acid (4-HB). Further provided is a method for the production of BDO. The method includes culturing a non-naturally occurring microbial biocatalyst, comprising a microbial organism having 4-hydroxybutanoic acid (4-HB) and 1,4-butanediol (BDO) biosynthetic pathways, the pathways including at least one exogenous nucleic acid encoding 4-hydroxybutanoate dehydrogenase, succinyl-CoA synthetase, CoA-dependent succinic semialdehyde dehydrogenase, 4-hydroxybutyrate:CoA transferase, 4-hydroxybutyrate kinase, phosphotranshydroxybutyrylase, ±-ketoglutarate decarboxylase, aldehyde dehydrogenase, alcohol dehydrogenase or an aldehyde/alcohol dehydrogenase for a sufficient period of time to produce 1,4-butanediol (BDO). The 4-HB and/or BDO products can be secreted into the culture medium.

    METHODS AND ORGANISMS FOR THE GROWTH-COUPLED PRODUCTION OF SUCCINATE
    23.
    发明公开
    METHODS AND ORGANISMS FOR THE GROWTH-COUPLED PRODUCTION OF SUCCINATE 审中-公开
    方法和机构琥珀酸生长偶联型生产

    公开(公告)号：EP1937821A2

    公开(公告)日：2008-07-02

    申请号：EP06824938.2

    申请日：2006-09-08

    Applicant: Genomatica, Inc.

    Inventor： BURGARD, Anthony, P. ,  VAN DIEN, Stephen, J.

    IPC: C12N15/74 ,  C12P19/02 ,  G01N33/50

    CPC classification number: C12N15/52 ,  C12N9/0006 ,  C12N9/001 ,  C12N9/1029 ,  C12N9/1205 ,  C12N9/1217 ,  C12N9/14 ,  C12P7/46

    Abstract: A non-naturally occurring microorganism comprising one or more gene disruptions encoding an enzyme associated with growth-coupled production of succinate when an activity of the enzyme is reduced, whereby the one or more disruptions confers stable growth-coupled production of succinate onto the non-naturally occurring microorganism is provided. The disruptions can be complete gene disruptions, and the non-naturally occurring organisms can include a variety of prokaryotic or eukaryotic microorganisms. A method of producing a non-naturally occurring microorganism having stable growth-coupled production of succinate is also provided. The method includes: (a) identifying in silico a set of metabolic modifications requiring succinate production during exponential growth, and (b) genetically modifying a microorganism to contain the set of metabolic modifications requiring succinate production.

    METHODS AND ORGANISMS FOR THE GROWTH-COUPLED PRODUCTION OF 1,4-BUTANEDIOL
    28.
    发明公开
    METHODS AND ORGANISMS FOR THE GROWTH-COUPLED PRODUCTION OF 1,4-BUTANEDIOL 有权
    方法和事业单位的1,4-丁二醇生长偶联型生产

    公开(公告)号：EP2185708A1

    公开(公告)日：2010-05-19

    申请号：EP08782639.2

    申请日：2008-08-06

    Applicant: Genomatica, Inc.

    Inventor： BURGARD, Anthony, P. ,  VAN DIEN, Stephen, J. ,  BURK, Mark, J.

    IPC: C12N15/52 ,  C12P7/18 ,  C12N1/00

    CPC classification number: C12P7/18 ,  B01D3/002 ,  C12N9/0006

    Abstract: The invention provides a non-naturally occurring microorganism comprising one or more gene disruptions, the one or more gene disruptions occurring in genes encoding an enzyme obligatory to coupling 1,4-butanediol production to growth of the microorganism when the gene disruption reduces an activity of the enzyme, whereby theone or more gene disruptions confers stable growth-coupled production of 1,4-butanediol onto the non-naturally occurring microorganism. The microorganism can further comprise a gene encoding an enzyme in a 1,4-butanediol (BDO) biosynthetic pathway. The invention additionally relates to methods of using microorganisms to produce BDO.

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